Amine neurotransmitters and their metabolites are studied in blood, cerebrospinal fluid (CSF), and urine to assess neurochemical alterations which may be associated with clinical diagnoses, clinical states, particular behavioral or psychopathological dimensions, or treatment with drugs. Because of both methodological advances in assays for low concentrations of metabolites and problems associated with the probenecid technique, CSF studies have focused increasingly on baseline (non-probenecid) lumbar punctures. A high pressure liquid chromatographic assay for monoamine neurotransmitters and their metabolites in blood, wine, and CSF was developed. Application of this assay to urinary measurements of norepinephrine and its metabolites provides an important new interpretation of the meaning of urinary 3-methoxy-4-dhydroxy-phenylglycol levels. Two further studies confirm previous reports of an association between low CSF 5-hydroxyindoleacetic acid and several measures of impulse dyscontrol. Drug response prediction studies based on pre-treatment metabolite levels continue.